Abstract:Fluorescence lifetime imaging microscopy (FLIM) provides detailed information about molecular interactions and biological processes. A major bottleneck for FLIM is image resolution at high acquisition speeds, due to the engineering and signal-processing limitations of time-resolved imaging technology. Here we present single-sample image-fusion upsampling (SiSIFUS), a data-fusion approach to computational FLIM super-resolution that combines measurements from a low-resolution time-resolved detector (that measures photon arrival time) and a high-resolution camera (that measures intensity only). To solve this otherwise ill-posed inverse retrieval problem, we introduce statistically informed priors that encode local and global dependencies between the two single-sample measurements. This bypasses the risk of out-of-distribution hallucination as in traditional data-driven approaches and delivers enhanced images compared for example to standard bilinear interpolation. The general approach laid out by SiSIFUS can be applied to other image super-resolution problems where two different datasets are available.